Cardiac Signs Good for New Diabetes Drug

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

An investigational agent (canagliflozin) for type 2 diabetes was generally well tolerated in patients at high risk of heart disease, although data on specific cardiovascular outcomes have not yet been released.

Genital mycotic infections were far more common with both doses of the drug, and there was a slightly higher incidence of urinary tract infection with the 300 mg dose.

BERLIN – An investigational agent for type 2 diabetes was generally well tolerated in patients at high risk of heart disease, although data on specific cardiovascular outcomes have not yet been released, researchers reported here.

In the CANVAS trial, the overall incidence of adverse events was similar across treatment and placebo groups, at about 60%, and events were mostly mild to moderate, David Matthews, MD, of Oxford, and colleagues reported at the European Association for the Study of Diabetes meeting here.

But the trial, which is set up to assess cardiovascular risk with canagliflozin, an investigational sodium glucose co-transporter (SGLT2) inhibitor, did not yet report cardiovascular outcome data, which remained blinded and is in the follow-up phase, the investigators said.

They conducted the ongoing Canagliflozin Cardiovascular Assessment Study (CANVAS), also known as DIA3008, to assess safety in 4,330 patients with type 2 diabetes considered to be at high risk of cardiovascular disease.

The current data come from an 18-week, preplanned substudy of 1,718 patients randomized to placebo or one of two daily doses of canagliflozin -- 100 mg or 300 mg -- in addition to their usual antidiabetic drug regimens.

The trial showed that patients on either dose of canagliflozin had significantly greater reductions in glycated hemoglobin A1c (HbA1c) levels than did those on placebo (-0.65% and -0.73% less than placebo for 100 and 300 mg, respectively, P<0.001 for both).

And the overall incidence of adverse events was similar across treatment groups, at 59%, 64%, and 65%, respectively.

Most of these events were mild to moderate in intensity, although the incidence of events leading to discontinuation was higher with the 300 mg dose of canagliflozin (5.3% versus 1.9% for both 100 mg and placebo).

Genital mycotic infections were far more common with both doses of the drug, and there was a slightly higher incidence of urinary tract infection with the 300 mg dose – both expected outcomes given that the main mechanism of action is an offloading of sugar directly into the urine, fueling bacterial growth.

Increased urination and hypotension were also more common with both doses of the drug. And the two doses of the drug carried more incidence of hypoglycemia compared with placebo (49% and 48% versus 37%).

The team has yet to report cardiovascular outcome data, which has remained blinded and is currently in a follow-up phase, they reported.

In terms of other efficacy outcomes, both doses of canagliflozin significantly lowered fasting plasma glucose (-1.3 mmol/L and -1.6 mmol/L compared with placebo, P<0.001 for both), and made patients lose more weight than placebo (-1.8 kg [4 lbs] and -2.3 kg [5 lbs], P<0.001 for both).

The drug also lowered systolic blood pressure compared with placebo, but not diastolic blood pressure.

And it raised all lipid parameters -- including LDL and triglycerides – although not always significantly.

Matthews said in a statement that the findings suggest the drug "could provide an important new treatment option for higher-risk adult patients with type 2 diabetes."

Canagliflozin is not yet approved in the U.S. or in Europe, but the European Medicines Agency has given the green light to another SGLT2 inhibitor, dapagliflozin (Forxiga) – which the FDA declined to do over concerns about increased risks of breast and bladder cancer with the agent.

Stefano Del Prato, MD, of the University of Pisa and vice president of EASD, said dapagliflozin hasn't yet been widely used in Europe, but the drug is appealing because it's a "unique tool to reduce glucose without manipulating insulin secretion and insulin sensitivity."

He said it's also "a way to improve the efficacy of other drugs," when used in combination.

The study was supported by Janssen.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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